Oxycodone addiction is widespread and pharmacological treatment is not presently available. Identification of molecular consequences that are the substrates of oxycodone addiction will help to devise therapeutic approaches to this psychiatric illness. We predict that exposure to extended oxycodone SA will be accompanied by escalation of drug intake and incubation of drug seeking after several days of forced abstinence. This will be accompanied by incubation of oxycodone seeking behaviors. These behavioral changes will also be accompanied by changes in mu, kappa and delta opioid receptor protein levels in the brains of rats exposed to the drug. Large doses of oxycodone may be necessary to cause changes in hippocampus-dependent learning and memory processes that might trigger psychiatric diatheses in humans addicted to opioids. These studies will identify which regional effects of oxycodone on the brain that will need to be taken into consideration when planning experiments that focus on the development of therapeutic interventions for oxycodone addiction.